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Single-Cell Genomics Decontamination with CellSweep

Caskey, M.; Rich, J.; Weber, R.; Mortazavi, A.; Pachter, L.; Hallgrimsdottir, I. B.

2026-03-06 bioinformatics
10.64898/2026.03.04.709349 bioRxiv
Show abstract

Single-cell genomics technologies enable high-throughput cell profiling, but technical contamination remains an obstacle to accurate downstream analysis. Free-floating ambient molecules released from lysed cells and global bulk contamination introduced during library preparation can distort molecular profiles. These artifacts can obscure cellular identities and reduce the reliability of differential analysis or clustering results. We present an efficient and effective approach to removing ambient and bulk contamination that can be applied to data generated from a wide variety of technologies. We show that our tool, CellSweep, outperforms other methods to remove artifacts using numerous benchmarks.

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